Method and electronic components for multi-functional electrical stimulation systems

ABSTRACT

A multi-functional electrical stimulation (ES) system adapted to yield output signals for effecting faradic, electromagnetic, or other forms of electrical stimulation for a broad spectrum of different biological and bio-medical applications. The system includes an ES signal stage having a selector coupled to a plurality of different signal generators, each generator producing a signal having a distinct shape such as a sine, a square or sawtooth wave or a simple or complex pulse form, the parameters of which are adjustable in regard to amplitude, duration, repetition rate and other variables. The signal from the selected generator in the ES stage is fed to at least one output stage where it is processed to produce a high or low voltage or current output of a desired polarity whereby the output stage is capable of yielding an electrical stimulation signal appropriate for its intended application. Also included in the system is a measuring stage which measures and displays the electrical stimulation signal operating on the substance being treated as well as the outputs of various sensors which sense conditions prevailing in this substance, whereby the user of the system can adjust it to yield an electrical stimulation signal of whatever type he wishes and can then observe the effects of this signal on a substance being treated.

RELATED APPLICATIONS

This application is a continuation of patent application serial number09/013,049, filed on Jan. 27, 1998, and now issued as U.S. Pat. No.6,029,090, the disclosure and drawings of which are incorporated hereinby reference.

This application is related to our provisional application S.N.60/034,869, filed on Jan. 27, 1997, entitled “ELECTRICAL STIMULATOR ANDAMPLIFIER”, the entire disclosure of which is incorporated herein byreference.

BACKGROUND OF INVENTION

1. Field of Invention

This invention relates generally to the electrical stimulation devicesfor effecting faradic, electromagnetic or other forms of electricalstimulation, and more particularly, to a multi-functional system forthis purpose capable of selectively yielding electrical stimulationsignals for a broad spectrum of different biological and bio-medicalapplications as well as for other applications, such as electrophoresis.

2. Status of Prior Art

Electrical stimulation (ES) is widely used in biological and bio-medicalresearch as well as in diagnostics and in clinical treatment. In faradicstimulation an intermittent or a continuous direct or alternatingcurrent or voltage is produced, whereas in electromagnetic stimulation,a current passing through a coil produces an electromagnetic field whosepattern depends on the wave form of the current.

Electrical stimulation is employed to effect nerve regeneration, inneuromuscular research, in medical diagnosis and treatment, and inpulsed voltage electrophoresis. Such stimulation is also used in bonehealing and in wound healing, as well as in pain relief by means oftranscutaneous electrical nerve stimulation (TENS). The use of ES toeffect nerve regeneration is disclosed in the Zanakis et al. patent4,774,967 as well as in the Borgens patent 4,919,140.

Researchers in the biological and medical sciences, physiotherapists,and clinicians who make use of ES require electrical stimulators of atype suitable for the activities in which they are engaged. Thusneurological investigators who seek to non-invasively stimulate deepnerves make use of commercially available magnetic stimulators whichproduce a high-intensity magnetic field pulse for this purpose.

Also commercially available are constant current stimulators for directcortical stimulation as well as electrical stimulators for nerve andmuscle stimulation procedures which generate single or double pulses, ortrains of such pulses. And commercially available are wave generatorscapable of selectively generating sine and square wave pulses suitablefor other types of electrical stimulation.

But what is not available to researchers and others who make use ofelectrical stimulation is a multi-functional system capable of yieldingan electrical stimulation signal that is appropriate for whateverbiological or biomedical application is the concern of the user of thesystem.

Let us assume, by way of example, that a researcher is engaged in aneurological research program in the course of which it becomesnecessary to conduct tests on the effects of many different types ofelectrical stimuli on a certain set of nerves. The researcher would thenhave to assemble from different commercial sources the severalelectrical stimulators of different types called for by this program.This burdensome requirement adds substantially to the cost of conductingthis research and to its space demands.

While the invention will be described herein as a system for producingelectrical stimulating signals, the signals produced thereby can also beused for electroporation, electrophoresis (preferably pulsed voltageelectrophoresis) and iontophoresis as well as for electrochemicalapplications as in the treatment of cancer in which a current is passedthrough the tissue being treated. The signals can also be used fortransdermal drug delivery.

SUMMARY OF INVENTION

In view of the foregoing, the main object of this invention is toprovide a multi-functional electrical stimulation (ES) system adapted toyield output signals for effecting faradic, electromagnetic or otherforms of electrical stimulation for a broad spectrum of differentbiological and biomedical applications.

A significant advantage of a system in accordance with the invention isthat it affords its user, whether a researcher, a diagnostician or aclinician, with whatever electrical stimulation signal is dictated bythe specific type of electrical stimulation that is required. Thus if inconducting tests, a researcher needs to subject certain nerves to manydifferent forms of electrical stimulation, the self-sufficient system,by itself and without accessories, is capable of supplying whateverelectrical stimulation signals are appropriate.

Also an object of this invention is to provide a multi-functional systemof the above type that includes a measuring stage that measures anddisplays the electrical stimulation signal operating on the substancebeing treated and also indicates and displays signals issuing fromsensors which sense conditions prevailing in the substance, such as pHand O₂, whereby the user of the system is able to observe and monitorthe effects of the electrical stimulation signal he has selected.

Another object of this invention is to provide a highly-compact systemof the above type which can be manufactured at relatively low cost.

Briefly stated, these objects are attained by a multi-functionalelectrical stimulation (ES) system adapted to yield output signals foreffecting faradic, electromagnetic or other forms of electricalstimulation for a broad spectrum of different biological and bio-medicalapplications. The system includes an ES signal stage having a selectorcoupled to a plurality of different signal generators, each producing asignal having a distinct shape such as a sine, a square or sawtoothwave, or a simple or complex pulse, the parameters of which areadjustable in regard to amplitude, duration, repetition rate and othervariables.

The signal from the selected generator in the ES stage is fed to atleast one output stage where it is processed to produce a high or lowvoltage or current output of a desired polarity whereby the output stageis capable of yielding an electrical stimulation signal appropriate forits intended application. Also included in the system is a measuringstage which measures and displays the electrical stimulation signaloperating on the substance being treated as well as the outputs ofvarious sensors which sense conditions prevailing in this substancewhereby the user of the system can manually adjust it or have itautomatically adjusted by feedback to provide an electrical stimulationsignal of whatever type he wishes and the user can then observe theeffect of this signal on a substance being treated.

In another embodiment of the system, the signals from the ES signalstage are put on a bus from which they can be accessed by the outputstages.

The electrical stimulation signal yielded by the system can be used forapplications other than those involving electrical stimulation, such asfor electrophoresis and electroporation. Or the signals from the systemcan be used in applications requiring mechanical or acoustic waves byapplying the signal to an appropriate transducer.

BRIEF DESCRIPTION OF DRAWINGS

For a better understanding of the invention, as well as other objectsand further features thereof, reference is made to the followingdetailed description to be read in conjunction with the accompanyingdrawing, wherein:

FIG. 1 is a block diagram of a system in accordance with the inventionhaving an ES stage, an output stage and a measuring stage;

FIG. 2 is a block diagram of a basic version of a system for producingvarious electrical stimulation pulses;

FIG. 3 illustrates an example of a preset custom module;

FIG. 4A is a graph showing at the full power output of an amplifier apulse having a rising edge;

FIG. 4B is a graph showing at the full power output of an amplifier apulse having a falling edge; and

FIG. 5 (Sections A & B) and FIG. 6 (Sections A & B), show an embodimentof a low voltage output stage for generating various analog pulses andtheir combinations from digital inputs.

DETAILED DESCRIPTION OF INVENTION

A system in accordance with the invention, as shown in FIG. 1, iscomposed of an ES signal stage 10 which at the user's discretiongenerates a faradic, an electromagnetic, or other type of electricalstimulation signal which is fed to an output stage 11. Output stage 11processes the electrical stimulation signals selected by the user toyield a stimulation signal suitable for its intended biological orbio-medical application.

Also provided is a measuring stage 12 which measures and displays theelectrical stimulation signal operating on the biological substancebeing subjected thereto, and/or its electrical parameters as well as theoutput of various sensors which sense conditions prevailing in thissubstance whereby the user is able to observe, monitor as well as toadjust the effects of the stimulation signal he has selected on thesubstance being treated.

ES signal stage 10 includes signal generators 13 to 17 producing signalsof different shape. Generator 13 is a pulse wave generator generatingone or more rectangular pulses, such as pulses A and B of differentwidth which can be outputted separately or can be added or subtractedfrom each other to yield A or B, A plus B or A minus B. Generator 14 isa sine wave generator, generator 15 generates a triangular or sawtoothwave, and generator 16 produces a ramp voltage wave. Generator 17 yieldsa wave of any arbitrary shape. The signal generators are capable ofgenerating a minimum one pulsatory signal or a greater numbers ofpulsatory signals, or of generating a gated signal with a minimum of oneperiod or a greater number of periods, with individual adjustments ofelectrical parameters.

By means of a serial input port 18 to ES stage 10 or a set of parallelinput ports 19, the parameters of the respective waves produced bysignal generators 13 to 17 can be adjusted in frequency, pulse width,amplitude and repetition rate, or with respect to any other variable.Coupled to generators 13 to 17 and activated by a signal applied theretoat terminal 20A is a mechanical or electronic selector switch 20. Theoutput signal from the signal generator selected by a switch 20 isapplied through a line 21 to output stage 11. In practice, the line ispreferably a bus system.

The ES signal stage 10 is preferably miniaturized and may take the formof a hybrid device or a single ASIC chip (Application SpecificIntegrated Circuit). Output stage 11 includes a mechanical or electronicselector switch 22 which applies the ES signal from stage 10 either to alow voltage processor 23, a high voltage processor 24, a currentprocessor 25, or a power processor 26 to put the ES signal in a formappropriate to the intended application for electrical stimulation. In apreferred version, all signals can be accessed simultaneously by one ormore output stages through a system bus. In practice, a combination ofone or more signal generators in the ES signal stage with one or more ofthe output stages can be miniaturized.

The output of the processor 23, 24, 25 or 26 chosen by selector switch22 is fed to a modulator 27 coupled to an amplitude control unit 28which modifies the amplitude of the signal applied thereto. The outputof amplitude-control unit 28 is applied to a polarity control unit 29 inwhich the electrical stimulation signal is given a positive or negativepolarity or is converted to an AC signal, depending on the intendedapplication for the electrical stimulation signal.

Each output stage can be configured with either multiple outputterminals 30 or with a single output. The multiple outputs make itpossible to run several parallel experiments or processes concurrently.

As previously mentioned, the ES system can be miniaturized to form asingle ES component comprising signal generators and miniaturized outputcircuitry packaged together. A functional sketch of one such EScomponent 31 is shown in FIG. 2, and an example of a customized module32 with a preset waveform and preset electrical parameters is shown inFIG. 3.

A preferred version of the ES component includes a sophisticated digitalpulse generator on a chip and an analog circuitry to define complexpulse patterns, with amplitudes up to ±10V. The output can be fed intoany number of desirable output stages, which can be integrated into thesame component or be independent proprietary devices, e.g., voltagecontrolled or current controlled output stages with variousvoltage/current amplitudes, high frequency output stage with variousbandwidths depending on a specific application, various power outputstages, etc. Waveforms other than pulse patterns, as well as modulatedsignals can be part of such a “system on a chip.”

The design of a digital ASIC consists of several blocks, which can beeither used together to create a sophisticated pulse generator forbiomedical applications, or can be used in any number of otherapplications requiring a pulse signal. Each of these blocks orfunctional modules can provide an independent waveform or pulse (Apulse; B pulse; square wave; time delay; etc). A basic one outputversion of the signal generator delivers two independent pulses A and Bwith digitally adjustable pulse widths, the same pulse repetition rate,and with an adjustable delay between them or for each of them. It alsodelivers a square wave and timing for alternate and biphasic pulses andtwo pulse trains. In a two or more output version, individual pulses canhave independently set repetition rates.

Several of these independent signal generators can be combined into amulti-output device. All timing parameters of the pulses preferably arefully programmable by a user via hardware or via software-generatedinputs. For example, one can adjust timing using thumbwheels or switchesconnected via parallel inputs of the ES component, or by using softwareand a serial, parallel, or custom interface as an input (or acombination of analog and digital inputs can be used). The ES componentcan include both a parallel and a serial interface so that the user candefine the optimal means for each application.

The analog output amplitudes of the ES component or ES system can beadjusted for each pulse separately (via hardware or software, as above).At the

same time, a specific DC level can be added; i.e., signal can be shiftedup or down from zero line. The alternate and biphasic pulses aredesigned so that only one adjustment for both positive and negativepulse width and amplitude is required, which results in guaranteedsymmetrical signals.

In the circuits shown in FIGS. 5 and 6 (sections A and B), the outputpreferably varies from 0 to ±10V and is set digitally. Rise time andfall time for a full power response in a standard speed implementationis 336 ns and 360 ns, respectively (see FIGS. 4A and 4B). For a 1.0Vpulse response, the corresponding numbers are 186 ns and 163 ns,respectively. The ES component can be also interfaced to a currentoutput stage with single or multiple outputs and current levels of ±200μA or another current level depending upon the particular application ofuse. In practice an isolated power supply for both analog and digitalsignals can be used.

An optional galvanic isolation can be added between the digital andanalog parts of the ES component using standard electronic components.This isolation system, in combination with an isolated power supply forthe analog signals, provides an isolated output from the stimulator.

1. Pulse Generation

This aspect of the invention is a detailed solution for generating fast,high accuracy analog pulses with predefined pulse amplitudes, as well asfor combining at least two single pulses to a pulse pattern. It is oneof possible specific solutions which can be implemented as a part of theoverall system design. The “Inputs and Outputs” section below can beviewed as a design example to show the concept behind creating an analogpulse pattern based on at least two pulse signals A and B. Each of the Aand B pulses has a separate setting of the pulse width and pulseamplitude. The same concept is used to create a highly accurate biphasicor alternating pulses based on a single amplitude setting for bothpositive and negative part of the signal and thus eliminating the riskfor an unbalanced charge delivered to the experimental system.

Digital pulses A and B have a pulse width TA and TB and a delay TDbetween them generated in hardware (or software) and together with thed-c voltages preset to the desired amplitudes for each pulse signalconstitute the input signals to this stage. The design depicted in the“Inputs and Outputs” section uses a voltage reference and two 12-bitDACs on the same chip to set carefully controlled d-c levels. Thedigital pulses A and B are used to control opening and closing of aswitch on the output of each of the DACS, respectively, and thus shapingA and B pulse waves. The correct amplitudes are set by the DACs and thecorrect analog pulse width is set by the length of time the appropriateanalog switch is closed. When the switch is open, the output voltage forA and B pulse, respectively, is set to zero. Both waveforms are thenpassed through an adding circuitry. A d-c level can be added at the sametime.

An optional set of preprogrammed modules, based on the architecture ofthe basic ES component, can be used independently or added to the basicES component or even made a part of the ASIC design; for example, apulse train used clinically for bone healing (timing parameters;repetition rate −15 Hz, pulse train length −5 ms, positive pulse with−200 us, negative pulse width −24 us, Electro-Biology, Inc. Parsippany,N.J.). This conventional bone-healing signal, measured with a pick-upcoil, is delivered from an electromagnetic field (EMF) stimulator. Apreprogrammed ES module allows for testing of the biological effects ofthe same or a similar electrical signal, but delivered throughelectrodes, without a strong magnetic field component, in addition to orinstead of both experimental and clinical use in EMF stimulators. Insituations with multiple parallel experiments, the cost of the equipmentpresently required will be significantly reduced by using pulsegenerator ASIC-based system of this invention rather than buying severalindependent stimulators.

The flexible pulse generator ASIC and the ES component of this inventioncan form the basis for an ES device as described herein, and can be usedby electrical stimulation equipment manufacturers as an inexpensiveoff-the-shelf component to simplify production, cut costs, save space,and miniaturize existing systems. The present invention improves theoverall system reliability by providing the whole system as a singlewell-tested component. The present invention using an ASIC reduces thepower requirements, thus permitting battery operation in applicationswhere high current/voltage output is not required, which also allows fora further miniaturization of the total digital/analog system and adds asafety feature for clinical applications.

The following are examples of signal generators that can be incorporatedin the ES signal stage 10, and the respective variable timing parametersof these generators:

I. Pulse Generator (a) Square pulse - repetition rate (50% duty cycle)(b) Single pulse A - repetition rate & pulse width (c) Dual pulses A andB - individually set pulse width; single output: same repetition ratefor both A and B; dual outputs: same or individually set repetitionrates (d) Alternate pulse - set automatically by setting pulse Aparameters (e) Biphasic pulse - set automatically by setting pulse Aparameters (f) A + B - same repetition rate for both individual pulsewidths (g) A − B - same repetition rate for both individual pulse widths(h) Pulse train - repetition rate of pulse train, and either pulse widthof the pulse train or number of individual pulses in the train (i) Userdefined - all applicable timing parameters II. Sinewave generator -frequency III. Sawtooth, triange, ramp frequency, rise and fall timeswaveform generators - IV. Arbitrary waveform generator - all timingparameters

Inputs and Outputs:

Referring now to FIG. 5, (Sections A & B) there are two, 2 mm, 40 pinheaders (P1 and P2) from which signal inputs, signal outputs, and powerconnect to the printed circuit board (pcb). The board requires twosupplies to operate, +15 VDC, and

−15 VDC. Power and Ground comes in through P2. +5 VDC necessary forlogic circuitry and interface is derived from onboard regulator U15 fromthe +15 VDC supply.

Referring now to FIG. 6A, pulse waveforms are generated within thestimulator by appropriate switching of 8 to 1 multiplexers U1, U2, U17,and U3. Logic level pulses TA, TB, SQ, TA1, and TA2 are selected byaddressing U1 and U2 with signals WV-A, WV-B, and WV-C. U17 and U3 setpulse polarity and select between UA and UB amplitudes.

TABLE 1 WV-A WV-B WV-C PULSE AMPLITUDE 0 0 0 Constant “ON” Constant UB 00 1 TA, “0” Pulsed TA = UA 0 1 0 TB, “0” Pulsed TB = UB 0 1 1 TA, TA2Pulsed TA = UA, TA2 = −UA 1 0 0 TA, TA1 Pulsed TA = UA, TA1 = −UA 1 0 1TA, TB Pulsed TA = UA, TB = −UB 1 1 0 TA, TB Pulsed TA = UA, TB = UB 1 11 SQ, “0” Pulsed SQ = UA

U4 and U5 comprise the “logic” which creates the waveform and routes theresultant signal to the output amplifiers. When the output of U1 pin 8is high, switch 1 of U5 is enabled, presenting the level determined byU17 to the output amplifiers, This also breaks switch 2 of U5 whichprevents contention with the output of U3. The level determined by U3pin 8 is presented to the output amplifiers when U1 pin 8 is low and U2pin 8 is high. When U1 pin 8 and U2 pin 8 are low, corresponding to nopulses, switch 4 of U5 is enabled, thereby shorting the input of theoutput amplifiers to ground. This discharges or resets the node to 0VDC.

Output Amplifiers:

The dual operation amplifier IC, U9, and associated passive componentscomprise the output amplifiers. Pin 2 of U9 is a summing junction.Pulses described above induce current through R3 into the inverting nodeof the first amplifier (pin 2). If DC-LEVEL is set, d-c voltageappearing at the junction of R4 and U8 pin 14 induces a d-c current intothe same inverting junction thereby creating a d-c voltage bias level atthe output. If DC-LEVEL is not set, R4 is grounded through switch 2 ofU8. No d-c bias appears at the output in this case. OUT1 is the outputof the first operational amplifier. This represents the inverted pulsedsignal output train. The second amplifier of U9 is also an inverterwhich provides a non-inverted pulse train. Switches 3 and 4 of U8 allowfor the polarity selection of OUT 2. A logic low selects thenon-inverting output. A logic high selects the inverted output. Uponselecting the inverting output illuminates LED 1.

D-C Level Circuits (FIG. 6B):

A 14 bit multiplying DAC, U6, operational amplifier U7, and associatedpassive components form the d-c level circuit. U6 is a current outputDAC configured for bipolar output. The VREF input is determined by thelevel of UA. Since UA ranges from 0 to +10V, the d-c level circuit canrange from 0 VDC to ±10 VDC. The 14-bit DAC bus interfaces directly toP1. Three control signals LVLDAC /LDAC, LVLDAC /CS, and LVLDAC /WR allowfor addressing the DAC and writing levels. Refer to the AD75538 datasheet, for more detailed information on this part.

Dual Programmable Reference:

Referring now to FIG. 5A, U14 is an accurate and stable +10,00 voltreference. Resistors R16 through R29 form a precision resistive dividerto derive 6 other voltage levels. U10 and U11 allow for the selection of+10,00V, 5.000V, 1.000V, 0.3000V, 0.2000V, 0.1000V, 0.0100V or groundfor the UA and UB channels. Signals UA_AO, UA_A1, UA_A2 (Table 2),UB_AO, UB_A1, and UB_A2 (Table 3) determine the UA and UB referencelevels respectively.

TABLE 2 UA_A0 UA_A1 UA_A2 LEVEL 0 0 0 10.00 V 0 0 1 5.000 V 0 1 0 1.000V 0 1 1 0.3000 V 1 0 0 0.2000 V 1 0 1 0.1000 V 1 1 0 0.0100 V 1 1 10.0000 V

TABLE 3 UB_A0 UB_A1 UB_A2 LEVEL 0 0 0 10.00 V 0 0 1 5.000 V 0 1 0 1.000V 0 1 1 0.3000 V 1 0 0 0.2000 V 1 0 1 0.1000 V 1 1 0 0.0100 V 1 1 10.0000 V

A dual op amp, U13, converts the DAC's A channel current output to +UAand −UA voltages. Likewise, U16 converts the DAC's B channel currentoutput to +UB and −UB voltages. U12 is a dual 12-bit multiplying DACarranged for unipolar outputs. U12 shares the same data bus (see FIGS.5B and 6B) as U6. It is addressed and controlled by the SAV _/CSA, SAV_/CSB, and SAV _/WRDAC signals. ±UA and ±UB are used by the waveformgenerating circuits to set signal amplitude and polarity. The UA levelis also used as the reference for the level DAC. Please refer to thedatasheets for the AD7538, AD7547, ADG408, ADG433, AD712, 78LO5, andLT1235 components.

Voltage Output Stage:

A ±10V voltage output is a generic output stage useful for severalneuromuscular and other applications. This output stage preferablyincludes an output amplifier stage sufficient to drive a load. A ±50Vvoltage output stage can be used in the alternative as a generic outputstage useful for several neuromuscular and other applications. It can belimited to a lower voltage than the maximum ±50V by choosing a lowervoltage power supply and changing values of appropriate components suchas resistors. This higher voltage output stage is especially useful forthe optimization of low voltage electroporation, and it can be packagedtogether with the ES component. Higher voltage output stages in therange up to 250V, or even higher up to 1,000V, or up to a few thousandvolts (preferable about 6,000V), and ranges therebetween, can be used(or can be specially useful) for pulsed voltage electrophoresis ormagnetic stimulation of the brain.

2. Magnetic Sensor Probe:

There is no good technique available on the market today to covermeasurements of both time varying and constant magnetic fields in therange of 0-10 Gauss, or higher (often used in biomedical experiments aswell as in clinical treatment—bone healing), and those that areavailable do not provide a reasonable bandwidth and resolution in threedirections simultaneously. Magnetoresistive sensors, such as thosepioneered by Honeywell, offer the various advantages over other forms ofmagnetic sensors, such as flux gates or coils: small dimensions, such asneeded in biomedical applications; high sensitivity, allowing for a longdistance between the item being sensed and the device (dependent on itsferromagnetic mass); immunity to electromagnetic noise and interferencesdue to the small internal impedance; and better reliability because itis a solid state solution with no moving parts; and lower developmentcosts because components can be easily incorporated into board-levelproducts.

A magnetic probe useful with the present invention is preferably a3-axis magnetic sensor working in the range of 0 to 10 Gauss, preferably0 to 20 Gauss, or 0 to 40 Gauss, with resolution better than 100 μGauss,and diameter of approximately 1 cm. Magnetoresistive transducers aremade of long strips of thin ferromagnetic films of material such as perMalloy, a nickel-iron alloy. These films are deposited and fabricatedusing standard semiconductor technology on silicon wafers. The stripsare several hundred Angstrom (150-500) in thickness, several tens ofmicrons wide (10-50) and several hundred to several thousand micronslong, and can be used to make the magnetic probe useful for thisinvention. An analog output magnetic sensor hybrid (e.g., model numberHMC2003, available from Honeywell) is a “building block” product thatallows to use an independent micro-controller, while obtaining theresolution and sensitivity of conventional magnetoresistive technology.(The Honeywell device comes in a small 20 pin 600 mil dual-in-linepackage that combines the magnetic sensing components with signalconditioning electronics and amplification for each channel.) To measurethe field range of 0-10 Gauss, used in some electromagnetic stimulationexperiments, and preferably 0-20 Gauss, the sensor can be used in aclosed mode operation. In a further embodiment, the probe includes theability to measure temperature. Another embodiment includes a miniature3-axis probe (<3 mm in diameter) with amplification. Both these sensorscan be utilized in both ac and dc mode.

3. System Overview:

Referring again to FIG. 1 showing the system composed of ES stage 10,output stage 11 and measuring stage 12, in using this system the userchooses the particular signal or waveform appropriate to the intendedelectrical stimulation application. The user uses a dial or switchesattached to the system or software communicating with the system, andsets up specific timing and amplitude parameters via the serial orparallel input ports 18 and 19. The user also selects output stage 11with either single or multiple output ports.

Measuring stage 12, by means of a sensor input terminal 12A, allows theuse of appropriate sensors to sense the electrical stimulation signalpassing through the organic substance being treated and environmentalparameters, such as current, magnetic field, voltage, impedance,temperature, pH, gas (O₂, CO₂, etc.) as well as various biochemicalsubstances involved locally in or resulting from the procedure at thesite where the signal is administered or at another site.

The various sensors for this purpose include sensing electrodes, pick-upcoils, temperature-sensitive devices, magnetic probes, and biosensors,all which yield a signal which is applied to input terminal 12A thisterminal is connected to a signal conditioner 33 whose output is coupledto a measuring and display unit 34 whose output is fed to a video screenor other indicator. Associated with unit 34 is a display control 35 anda DMM control 36.

General System Features:

As ES system in accordance with the invention consists of a digital,high accuracy pulse generator capable of generating several eitherdependent or independent, synchronized rectangular pulses, availablesimultaneously, through a selector or preferably on a system bus. One ormore output stages (identical or different) can be placed anywhere onthe system bus and be accessed by a user. The choice the user makes maybe threefold; either one specific output stage is plugged into thesystem; a specific output stage is selected among several output stagesavailable using either a dial, a selector, or other means; or severaloutput stages are used in parallel, either independently or triggered byeach other.

The ES system can be also triggered by an external process or event,e.g., a physiological event, and will deliver either a preset signal inresponse to such a stimuli, or a signal which can be continuouslymodified by a triggering signal with respect to both timing andamplitude (and possibly shape). A preset delay between a triggeringsignal and a response signal can be made available.

Signals other than pulses can also be made available and accessibleeither through a selector or on the bus, including gated and/ormodulated signals of various shapes. All of the signals can be fed tothe output stages in the following ways: one signal to one output stage(with a single or multiple outputs); one signal to several output stages(identical or different); several signals to one output stage (for acomplex signal shape or in case of multiple outputs); several signals toseveral output stages (identical or different).

Several, simple or complex rectangular pulses and other signals areavailable, for the output stages, through a selector or preferably onthe bus. These signals are synchronized and can be accessed by an outputstage either by selecting only one signal or by accessing severalsignals at the same time. In the latter case the signals can be combinedin the output stage to a more complex pattern. In either case, they canbe accessed by a single selected output stage or simultaneously byseveral, either identical or different, output stages.

By having a number of signals accessible on the bus, output stages canhave simultaneous access to identical or different signals creating thefollowing system configurations:

A. one selected output stage (either voltage—low or high, current—low orhigh, or power) with a single output producing a simple signal; oneselected output stage with a single output producing a complex signalpattern;

B. one selected output stage with multiple identical outputs (eithervoltage—low or high, current—low or high, or power) with the same shapesignals and identical electrical parameters; one selected output stagewith multiple identical outputs with the same shape signals withdifferent amplitudes only;

C. multiple identical output stages (either voltage—low or high,current—low or high, or power) with the same shape signals withidentical electrical parameters; multiple identical output stages withthe same shape signals with different amplitudes; multiple identicaloutput stages with the same shape signals with different timing;multiple identical output stages the same shape signals with differentamplitude and timing;

D. multiple identical output stages with different shape signals withall the options from above;

E. multiple identical output stages producing signals with eitheridentical or different complex patterns with all the options from above;

F. multiple different output stages, e.g., a low voltage single outputstage and multiple output current output stage, or a power output stage,producing the same shape signals with identical timing; multipledifferent output stages, producing the same shape signals with differenttiming; multiple different output stages, producing different shapesignals with identical timing; multiple different output stages,producing different shape signals with different timing.

While there have been shown and described preferred embodiments of amulti-functional electrical stimulation system in accordance with theinvention, it will be appreciated that many changes may be made thereinwithin the spirit of the invention.

I claim:
 1. A method of producing an output signal for effectingfaradic, electromagnetic, and/or other forms of electrical stimulationfor any of a broad spectrum of biological and biomedical applications,the method comprising the steps of: (a) generating a plurality ofsignals, wherein each signal has a predetermined waveform and at leastone of the signals comprises pulses; (b) adjusting one or moreelectrical parameters of at least one signal, wherein the parametersinclude any of: amplitude, frequency, shape, timing parameters, phase,pulse duration, and pulse repetition rate; and (c) selecting as anoutput signal one or more of the generated and adjusted signals, whereinthe selection is based upon an intended stimulation application.
 2. Themethod of claim 1 wherein the plurality of signals includes at least onesine wave.
 3. The method of claim 1 wherein the plurality of signalsincludes at least one square wave.
 4. The method of claim 1 wherein theplurality of signals includes at least one sawtooth wave.
 5. The methodof claim 1 wherein step (b) is performed using a serial data port. 6.The method of claim 1 wherein step (b) is performed using a paralleldata port.
 7. The method of claim 1 further including the step ofprocessing the output signal to yield a processed output signalappropriate for an intended application.
 8. The method of claim 7wherein the step of processing includes the step of producing any of ahigh-current output, a low current output, a high-voltage output, and alow-voltage output.
 9. The method of claim 7 further including the stepof measuring the processed output signal.
 10. The method of claim 9further including the step of displaying the processed output signal.11. The method of claim 9 further including the step of providing asignal generating mechanism, a signal measuring mechanism, and a signalprocessing mechanism on an integrated circuit, a hybrid circuit, and/oras an electronic component.
 12. The method of claim 7 further includingthe steps of measuring the processed output signal being applied to amedium undergoing a treatment process.
 13. The method of claim 7 furtherincluding the step of utilizing one or more sensors to sense conditionsprevailing in a medium.
 14. The method of claim 13 further including thestep of sensing pH in the medium.
 15. The method of claim 13 furtherincluding the step of sensing oxygen gas concentration in the medium.16. The method of claim 13 further including the step of sensingconcentration of a gaseous substance in the medium.
 17. The method ofclaim 13 further including the step of utilizing the one or more sensorsto provide feedback for adjusting the one or more electrical parametersof the at least one signal.
 18. The method of claim 17 further includingthe step of providing a signal generating mechanism and a signalprocessing mechanism on an integrated circuit, a hybrid circuit, or asan electronic component.
 19. The method of claim 13 wherein the sensorscomprise any of sensing electrodes, pickup coils, temperature sensitivedevices, magnetic probes, and biosensors.
 20. The method of claim 13further including the step of sensing presence of a predeterminedgaseous substance in the medium.
 21. The method of claim 13 furtherincluding the step of sensing partial pressure of oxygen gas in themedium.
 22. The method of claim 13 further including the step of sensingpartial pressure of carbon dioxide gas in the medium.
 23. The method ofclaim 13 further including the step of measuring the sensor signal. 24.The method of claim 23 further including the step of providing a signalgenerating mechanism, a signal measuring mechanism, and a signalprocessing mechanism on an integrated circuit, a hybrid circuit, and/oras an electronic component.
 25. The method of claim 7 further includingthe step of providing a signal generating mechanism and a signalprocessing mechanism on an integrated circuit, a hybrid circuit, or asan electronic component.
 26. The method of claim 1 further including thestep of combining an adjusted signal with at least one generated signalto provide an output signal.
 27. The method of claim 1 further includingthe step of combining two or more adjusted signals to provide an outputsignal.
 28. The method of claim 1 further including the step ofcombining two or more generated signals to provide an output signal. 29.The method of claim 1 further including the step of placing a pluralityof adjusted signals on a bus.
 30. The method of claim 29 furtherincluding the step of selecting one or more desired adjusted signalsfrom a plurality of adjusted signals on the bus.
 31. The method of claim1 further including the step of providing a signal generating mechanismon an integrated circuit, a hybrid circuit, or as an electroniccomponent.
 32. The method of claim 1 further including the step ofplacing a plurality of digital adjustment signals on a bus, the digitaladjustment signals providing for adjustment of one or more of thegenerated signals.
 33. An electronic component equipped to produce anoutput signal for effecting faradic, electromagnetic, and/or other formsof electrical stimulation for any of a broad spectrum of biological andbiomedical applications, the component comprising: (a) a plurality ofsignal generators, wherein each signal generator produces apredetermined waveform; (b) an adjustment port for accepting an inputsignal specifying an adjustment of one or more electrical parameters ofat least one predetermined waveform, wherein the parameters include anyof: amplitude, frequency, shape, timing parameters, phase, pulseduration, and pulse repetition rate; (c) at least one output port; and(d) a selecting mechanism for applying to the output port an outputsignal comprising one or more of the generated and adjusted signals,wherein the selection is based upon an intended stimulation application.34. The electronic component of claim 33 wherein at least one of thepredetermined waveforms comprises pulses.
 35. The electronic componentof claim 33 further including a combining mechanism for combining two ormore adjusted signals to provide the output signal.
 36. The electroniccomponent of claim 33 further including a combining mechanism forcombining an adjusted signal with at least one generated signal toprovide an output signal.
 37. The electronic component of claim 33further including a combining mechanism for combining two or moregenerated signals to provide an output signal.
 38. The electroniccomponent of claim 33 further including a port for accepting a signalfrom one or more sensors that sense conditions prevailing in the medium.39. The electronic component of claim 38 wherein the sensors compriseany of sensing electrodes, pickup coils, temperature sensitive devices,magnetic probes, and biosensors.
 40. The electronic component of claim33 further including a mechanism for placing a plurality of adjustedsignals on a bus.
 41. The electronic component of claim 40 for use witha selection mechanism that selects one or more desired adjusted signalsfrom a plurality of adjusted signals on the bus.
 42. The electroniccomponent of claim 33 further including a signal measuring port equippedto accept input signals from one or more signal measuring mechanisms.43. The electronic component of claim 42 wherein the one or more signalmeasuring mechanisms include one or more sensors.
 44. The electroniccomponent of claim 43 wherein the one or more sensors are used toprovide a feedback signal for adjusting the one or more electricalparameters of the at least one signal.
 45. The electronic component ofclaim 44 wherein the one or more sensors include any of sensingelectrodes, pickup coils, temperature sensitive devices, magneticprobes, and biosensors.
 46. The electronic component of claim 33 whereinthe output port is coupled to an output bus, wherein the electroniccomponent is equipped to place any of a plurality of adjusted signals onthe output bus.
 47. The electronic component of claim 46 wherein theelectronic component places a plurality of adjusted signals on theoutput bus.
 48. A method of producing an output signal for effectingfaradic, electromagnetic, and/or other forms of electrical stimulationfor any of a broad spectrum of biological and biomedical applications,the method comprising the steps of: (a) controlling generation of aplurality of signals, wherein each signal has a predetermined waveform,such that one or more electrical parameters of at least one signal iscontrolled, wherein the parameters include any of: amplitude, frequency,shape, timing parameters, phase, pulse duration, and pulse repetitionrate; and (b) selecting as an output signal one or more of the generatedsignals, wherein the selection is based upon an intended stimulationapplication.
 49. An electronic component equipped to produce an outputsignal for effecting faradic, electromagnetic, and/or other forms ofelectrical stimulation for any of a broad spectrum of biological andbiomedical applications, the electronic component comprising: (a) acontrolling mechanism for controlling generation of a plurality ofsignals, wherein each signal has a predetermined waveform, such that oneor more electrical parameters of at least one signal is controlled,wherein the parameters include any of amplitude, frequency, shape,timing parameters, phase, pulse duration, and pulse repetition rate; and(b) a selection mechanism for selecting as an output signal one or moreof the generated signals, wherein the selection is based upon anintended stimulation application.
 50. The electronic component of claim49 wherein at least one of the predetermined waveforms comprises pulses.51. The electronic component of claim 49 further including a combiningmechanism for combining two or more adjusted signals to provide theoutput signal.
 52. The electronic component of claim 49 furtherincluding a combining mechanism for combining an adjusted signal with atleast one generated signal to provide an output signal.
 53. Theelectronic component of claim 49 further including a combining mechanismfor combining two or more generated signals to provide an output signal.54. The electronic component of claim 49 further including a port foraccepting a signal from one or more sensors that sense conditionsprevailing in a medium.
 55. The electronic component of claim 54 whereinthe sensors comprise any of sensing electrodes, pickup coils,temperature sensitive devices, magnetic probes, and biosensors.
 56. Theelectronic component of claim 49 further including a mechanism forplacing a plurality of adjusted signals on a bus.
 57. The electroniccomponent of claim 56 for use with a selection mechanism that selectsone or more desired adjusted signals from a plurality of adjustedsignals on the bus.
 58. The electronic component of claim 49 furtherincluding a signal measuring port equipped to accept input signals fromone or more signal measuring mechanisms.
 59. The electronic component ofclaim 58 wherein the one or more signal measuring mechanisms include oneor more sensors.
 60. The electronic component of claim 59 wherein theone or more sensors are used to provide a feedback signal for adjustingthe one or more electrical parameters of the at least one signal. 61.The electronic component of claim 60 wherein the one or more sensorsinclude any of sensing electrodes, pickup coils, temperature sensitivedevices, magnetic probes, and biosensors.
 62. The electronic componentof claim 49 wherein the output port is coupled to an output bus, whereinthe electronic component is equipped to place any of a plurality ofadjusted signals on the output bus.
 63. The electronic component ofclaim 62 wherein the electronic component places a plurality of adjustedsignals on the output bus.
 64. An electronic component equipped toproduce an output signal, the electronic component comprising: (a) acontrolling mechanism for controlling generation of a plurality ofsignals, wherein each signal has a predetermined waveform, such that oneor more electrical parameters of at least one signal is controlled,wherein the parameters include any of: amplitude, frequency, shape,timing parameters, phase, pulse duration, and pulse repetition rate; and(b) a selection mechanism for selecting as an output signal one or moreof the generated signals.
 65. The electronic component of claim 64wherein at least one of the predetermined waveforms comprises pulses.66. The electronic component of claim 64 further including a combiningmechanism for combining two or more adjusted signals to provide theoutput signal.
 67. The electronic component of claim 64 furtherincluding a combining mechanism for combining an adjusted signal with atleast one generated signal to provide an output signal.
 68. Theelectronic component of claim 64 further including a combining mechanismfor combining two or more generated signals to provide an output signal.69. The electronic component of claim 64 further including a port foraccepting a signal from one or more sensors that sense conditionsprevailing in the medium.
 70. The electronic component of claim 69wherein the sensors comprise any of sensing electrodes, pickup coils,temperature sensitive devices, magnetic probes, and biosensors.
 71. Theelectronic component of claim 70 wherein the electronic component placesa plurality of adjusted signals on the output bus.
 72. The electroniccomponent of claim 64 further including a mechanism for placing aplurality of adjusted signals on a bus.
 73. The electronic component ofclaim 72 for use with a selection mechanism that selects one or moredesired adjusted signals from a plurality of adjusted signals on thebus.
 74. The electronic component of claim 64 further including a signalmeasuring port equipped to accept input signals from one or more signalmeasuring mechanisms.
 75. The electronic component of claim 74 whereinthe one or more signal measuring mechanisms include one or more sensors.76. The electronic component of claim 75 wherein the one or more sensorsare used to provide a feedback signal for adjusting the one or moreelectrical parameters of the at least one signal.
 77. The electroniccomponent of claim 76 wherein the one or more sensors include any ofsensing electrodes, pickup coils, temperature sensitive devices,magnetic probes, and biosensors.
 78. The electronic component of claim64 wherein the output port is coupled to an output bus, wherein theelectronic component is equipped to place any of a plurality of adjustedsignals on the output bus.
 79. An integrated circuit equipped to producean output signal for effecting faradic, electromagnetic, and/or otherforms of electrical stimulation for any of a broad spectrum ofbiological and biomedical applications, the integrated circuitcomprising: (a) a plurality of signal generators, wherein each signalgenerator produces a predetermined waveform; (b) an adjustment port foraccepting an input signal specifying an adjustment of one or moreelectrical parameters of at least one predetermined waveform, whereinthe parameters include any of: amplitude, frequency, shape, timingparameters, phase, pulse duration, and pulse repetition rate; (c) atleast one output port; and (d) a selecting mechanism for applying to theoutput port an output signal comprising one or more of the generated andadjusted signals, wherein the selection is based upon an intendedstimulation application.
 80. The integrated circuit of claim 79 whereinat least one of the predetermined waveforms comprises pulses.
 81. Theintegrated circuit of claim 79 further including a combining mechanismfor combining two or more adjusted signals to provide the output signal.82. The integrated circuit of claim 79 further including a combiningmechanism for combining an adjusted signal with at least one generatedsignal to provide an output signal.
 83. The integrated circuit of claim79 further including a combining mechanism for combining two or moregenerated signals to provide an output signal.
 84. The integratedcircuit of claim 79 further including a port for accepting a signal fromone or more sensors that sense conditions prevailing in the medium. 85.The integrated circuit of claim 84 wherein the sensors comprise any ofsensing electrodes, pickup coils, temperature sensitive devices,magnetic probes, and biosensors.
 86. The integrated circuit of claim 84wherein the integrated circuit places a plurality of adjusted signals onthe output bus.
 87. The integrated circuit of claim 79 further includinga mechanism for placing a plurality of adjusted signals on a bus. 88.The integrated circuit of claim 87 for use with a selection mechanismthat selects one or more desired adjusted signals from a plurality ofadjusted signals on the bus.
 89. The integrated circuit of claim 79further including a signal measuring port equipped to accept inputsignals from one or more signal measuring mechanisms.
 90. The integratedcircuit of claim 89 wherein the one or more signal measuring mechanismsinclude one or more sensors.
 91. The integrated circuit of claim 90wherein the one or more sensors are used to provide a feedback signalfor adjusting the one or more electrical parameters of the at least onesignal.
 92. The integrated circuit of claim 91 wherein the one or moresensors include any of sensing electrodes, pickup coils, temperaturesensitive devices, magnetic probes, and biosensors.
 93. The integratedcircuit of claim 79 wherein the output port is coupled to an output bus,wherein the integrated circuit is equipped to place any of a pluralityof adjusted signals on the output bus.
 94. A hybrid circuit equipped toproduce an output signal for effecting faradic, electromagnetic, and/orother forms of electrical stimulation for any of a broad spectrum ofbiological and biomedical applications; wherein the hybrid circuitcomprises at least one digital component and at least one analogcomponent integrated onto a common substrate; the hybrid circuit furthercomprising: (a) a plurality of signal generators, wherein each signalgenerator produces a predetermined waveform; (b) an adjustment port foraccepting an input signal specifying an adjustment of one or moreelectrical parameters of at least one predetermined waveform, whereinthe parameters include any of: amplitude, frequency, shape, timingparameters, phase, pulse duration, and pulse repetition rate; at leastone output port; and (c) a selecting mechanism for applying to theoutput port an output signal comprising one or more of the generated andadjusted signals, wherein the selection is based upon an intendedstimulation application.
 95. The hybrid circuit of claim 94 wherein atleast one of the predetermined waveforms comprises pulses.
 96. Thehybrid circuit of claim 94 further including a combining mechanism forcombining two or more adjusted signals to provide the output signal. 97.The hybrid circuit of claim 94 further including a combining mechanismfor combining an adjusted signal with at least one generated signal toprovide an output signal.
 98. The hybrid circuit of claim 94 furtherincluding a combining mechanism for combining two or more generatedsignals to provide an output signal.
 99. The hybrid circuit of claim 94further including a port for accepting a signal from one or more sensorsthat sense conditions prevailing in the medium.
 100. The hybrid circuitof claim 99 wherein the sensors comprise any of sensing electrodes,pickup coils, temperature sensitive devices, magnetic probes, andbiosensors.
 101. The hybrid circuit of claim 100 wherein the hybridcircuit places a plurality of adjusted signals on the output bus. 102.The hybrid circuit of claim 94 further including a mechanism for placinga plurality of adjusted signals on a bus.
 103. The hybrid circuit ofclaim 102 for use with a selection mechanism that selects one or moredesired adjusted signals from a plurality of adjusted signals on thebus.
 104. The hybrid circuit of claim 94 further including a signalmeasuring port equipped to accept input signals from one or more signalmeasuring mechanisms.
 105. The hybrid circuit of claim 104 wherein theone or more signal measuring mechanisms include one or more sensors.106. The hybrid circuit of claim 105 wherein the one or more sensors areused to provide a feedback signal for adjusting the one or moreelectrical parameters of the at least one signal.
 107. The hybridcircuit of claim 106 wherein the one or more sensors include any ofsensing electrodes, pickup coils, temperature sensitive devices,magnetic probes, and biosensors.
 108. The hybrid circuit of claim 94wherein the output port is coupled to an output bus, wherein theelectronic component is equipped to place any of a plurality of adjustedsignals on the output bus.